1. Field of the Invention
The invention relates to a gel formulation of tretinoin (all trans-retinoic acid, or vitamin A acid). More particularly, it relates to gel formulations of tretinoin which are effective when tretinoin is present in low concentrations. The product is particularly suitable for treating such dermatological disorders as acne vulgaris.
2. Description of the Prior Art
Acne vulgaris is a dermatological disorder prevalent in adolescence. It appears most commonly on the face and trunk of the patient. The basic lesion of acne is the comedo or "blackhead" of a pilosebaceous follicle. In its mildest form, only few comedones are present, but in its severe form, a multiplicity of severe, persistent comedones are present. Permanent scarring is frequently a consequence of the severe form of acne.
Acne occurs when there is a filling up of the follicle with a rather tough keratinous material. This impaction of horny material is the whitehead and blackhead. As a result of bacterial growth in these horny impactions, the follicle ruptures, initiating the inflammatory phase of the disease which takes the form of pustules, papules, cysts and nodules.
A variety of methods have been used for the treatment of acne, including the use of peeling agents, hormone therapy for female patients, antibacterial therapy and general surgical skin planing.
Although the systemic administration of hormones and antibacterials have been used with some success, until recently none of the topical treatments have been particularly effective.
Vitamin A acid (tretinoin) has been applied topically, (Beer, Von P., "Untersuchungen uber die Wirkung der Vitamin A-Saure," Dermatologica, 124: 192-195, March, 1962 and Stuttgen, G., "Zur Lakalbehandlung von Keratosen mit Vitamin A-Saure," Dermatologica, 124: 65-80, February, 1962) in those hyperkeratotic disorders which are responsive to high oral doses of Vitamin A. Among those treated by Beer and Stuttgen were patients with acne; however, these investigators reported no effective results with Vitamin A acid on acne. British Pat. No. 906,000 disclosed a cosmetic preparation containing Vitamin A acid for the regulation of the cornification processes of human skin, but no mention is made of the use of such preparation for the treatment of acne.
Recently, however, it has been demonstrated that prolonged topical application of Vitamin A acid is effective in the treatment of acne (Kligman, A. M., "Topical Vitamin A acid in Acne Vulgaris," Arch Derm., 99: 469-476 April 1969). Kligman utilizes a composition in which Vitamin A acid is dispersed in a water-miscible (substantially oil- and fat-free) liquid carrier having high solvating action. The topical application of this Vitamin A acid composition causes irritation of the skin in the treated areas. See U.S. Pat. No. 3,729,568 issued Apr. 24, 1973 to Albert M. Kligman.
More recently, it has been found that acne can be effectively treated with a cream formulation containing tretinoin, or Vitamin A acid. A cream formulation is generally more acceptable to patients than the liquid vehicle from the point of view of aesthetics and ease of application. Moreover, another important advantage of the cream form of tretinoin is that it reduces the side effects normally associated with the topical application of tretinoin. These side effects, erythema, stinging and itching, may be sufficient to cause the patient to discontinue the application of tretinoin before it can be fully effective upon the acne.
Notwithstanding these advantages, cream formulations containing tretinoin possess some undesirable attributes. One of these undesirable attributes is the difficulty in uniformly applying sufficient amounts of the active ingredient to the lesion of acne to be effective and at the same time avoid local excesses, surface spread or pooling into facial creases, the nasolabial folds and corners of the mouth where the cream may cause erythema, stinging and itching. Another undesirable attribute of cream formulations of tretinoin is their relative instability, often necessitating the use of refrigeration or antimicrobial preservatives to prevent microbiological contamination, as well as special additives to maintain physical stability.
It is, therefore, an object of the present invention to provide a vehicle for tretinoin from which tretinoin is readily available for absorption by the skin.
It is a further object to provide an acne treatment composition which is effective at low concentrations of tretinoin, so as to avoid side effects associated with the use of acne treatment formulations having high concentrations of tretinoin.
It is another object of the invention to provide gel formulations of tretinoin which possess good physical and chemical stability without refrigeration and without special additives or antimicrobial preservatives.
It is still another object to provide gel formulations having such other desirable qualities as being cosmetically elegant, having a perceptible drying effect or at least making no contributions to the oiliness of acne patients' skin, and allowing accurate application of effective amounts of tretinoin to the acne lesion.
These and other objects of the present invention will be more fully understood in the light of the specific examples and description set forth hereinafter.